Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma

Xiao-Yan Wang; Narasimha M Beeraka; Nan-Nan Xue; Hui-Ming Yu; Ya Yang; Mao-Xing Liu; Vladimir N Nikolenko; Jun-Qi Liu; Di Zhao

doi:10.5306/wjco.v14.i1.13

Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma

World J Clin Oncol. 2023 Jan 24;14(1):13-26. doi: 10.5306/wjco.v14.i1.13.

Authors

Xiao-Yan Wang¹, Narasimha M Beeraka^{2

3

4}, Nan-Nan Xue², Hui-Ming Yu⁵, Ya Yang², Mao-Xing Liu⁶, Vladimir N Nikolenko^{3

7}, Jun-Qi Liu², Di Zhao⁸

Affiliations

¹ Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
² Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
³ Department of Human Anatomy, I. M. Sechenov First Moscow State Medical University, Moscow 119991, Russia.
⁴ Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Mysuru 570015, India.
⁵ Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 065005, China.
⁶ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing, China.
⁷ M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
⁸ Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China. zhaodi0110@126.com.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens. The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.

Aim: To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.

Methods: Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The edgeR, a Bioconductor package, was used to analyze mRNA expression between different groups. We screened genes specifically responsible for radioresistance to estimate overall survival. Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other. Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation of βi and risk score using the following formula: .

Results: We identified three prognostic mRNAs (cathepsin S [CTSS], cluster of differentiation 180 [CD180], and SLP adapter and CSK-interacting membrane protein [SCIMP]) indicative of radioresistance. The expression of the three identified mRNAs was related to each other (r > 0.70 and P < 0.05). As to 1-year and 3-year overall survival prediction, the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841, respectively. When stratifying patients based on the risk score derived from the signature, the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group (P < 0.0001). Overall survival of the low-risk patients was significantly better than that of the high-risk patients (P = 0.018).

Conclusion: We have developed a novel three-gene prognostic signature consisting of CTSS, CD180, and SCIMO for ESCC, which may facilitate the prediction of early prognosis of this malignancy.

Keywords: CD180; CTSS; Esophageal squamous cell carcinoma; Prognosis; Radioresistance; SCIMP; TNM stage.